C5AR ANTAGONIST PMX53 (C15-1305-138)

General description

A cell-permeable, orally available, and metabolically stable macrocyclic hexapeptidomimetic compound that acts as a non-competitive antagonist of complement C5a receptor (C5aR; CD88; IC₅₀ = 240 nM) and as a low-affinity agonist for MrgX2, a GPCR, in human mast cells Shown to specifically bind to C5aR1 and not to CaR2 and C3aR. Displays a broad range of anti-inflammatory effects, both in vitro and in vivo. Shown to inhibit C5a-induced neutrophil myeloperoxidase release (IC₅₀ = 22 nM) and chemotaxis (IC₅₀ = 75 nM). Preincubation with PMX-53 (~10 nM) blocks C5a-induced Ca2+ responses in HMC-1 and RBL-2H3 cells, but does not affect C3a responses. Suppresses the growth of 4T1 mammary carcinoma tumor xenograft in mice (1 mg/kg/every 2-3 days, s.c.). Reported to diminish C5a-mediated increase in pluripotency in human embryonic stem cells in the absence of FGF2.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
C5aR

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Sequence

Ac-Phe-[Orn-Pro-dCha-Trp-Arg]

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Lillegard, K., et al. 2014. JPET.351,344.
Vadrevu, S. K., et al. 2014. Cancer Res.74, 3454.
Liang, S., et al. 2011. J. Immun.186, 869.
Woodruff, T., et al. 2005. JPET.314, 811.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Molecular Weight: 896.09 (free base basis). Empirical Formula: C₄₇H₆₅N₁₁O₇ · xC₂HF₃O₂. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: off-white. solubility: DMSO: 50 . mg/mL. storage temp.: 2-8°C. Storage Class Code: 13 - Non Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.